The home side won the Andorran top flight with 66 points from 27 games, while the visitors currently have one point in Denmark's premier division after one matchweek.
Match preview
The hosts had to overcome KF Ballkani on penalties on July 16 to reach the second round of the Champions League qualifiers.
The tie itself was tense, with Santa Coloma reversing a 2-1 first-leg deficit and the scoreline read 3-3 after extra time.
Indeed, the home side were on the brink of elimination before Walid Hamidi's own goal gave them a 1-0 lead in the 92nd minute, although Coloma will be disappointed that they were taken to penalties by Ballkani considering they had been playing with 10 men since the 37th minute.
The hosts will have been thrilled with their domestic campaign as their league title win in 2023-24 was the first in their history.
Manager Boris Anton's side won the league having scored 57 goals and conceded 12, and this was the division's fourth best offensive and best defensive records respectively.
The Squirrels have been difficult to beat at home and they have lost just twice in 19 matches at Estadi Nacional, winning 12 of these fixtures.
Opponents Midtjylland did not play in the first Champions League qualifying round, and are entering the competition at the second stage as they won their domestic league in the 2023-24 season.
Their title winning campaign saw them finish first in the regular season with 48 points from 22 games, and after topping their championship playoff group they ended the overall season with 63 points from 32 matches.
Last season, the Wolves scored a total of 62 goals and conceded 43 times, and this made them the division's second best offensive and fifth best defensive side.
Midtjylland's 2024-25 top-flight campaign has already begun, and in their opening game they drew 1-1 with Aarhus on July 19.
Manager Thomas Thomasberg has been in charge since March 2023, and this is his second spell as boss after previously coaching the side between 2008 and 2009.
Thomasberg's win rate of 57% with Midtjylland is the second highest he has achieved in his career to date, only surpassed by his stint at Hjorring, who he briefly coached between January 2010 and June 2010.
UE Santa Coloma Champions League form:
L
W
FC Midtjylland form (all competitions):
Team News
Although Chete, Marcos Blasco, Pablo Molina, Andreas Mohedano, Jorge and Bilal El Bakkali were all subbed off in the hosts' last match against Ballkani, they have avoided picking up any serious injuries.
As such, expect manager Anton to field a similar side on Tuesday, with Christian Garcia likely to partner Chete in the heart of defence.
Meanwhile, the visitors have several absentees including, Mikel Gogorza and Valdemar Byskov, who are away at the Under-19 Euros, while Emiliano Martinez is yet to return after his Copa America campaign with Uruguay.
Elsewhere, Gue-sung Cho is set to be out until August due to a knee injury, while Marrony is likely to miss the rest of the season as a result of a knee issue.
Left-back Paulinho was also taken off against Aarhus on July 19, and is a doubt for Tuesday's clash.
UE Santa Coloma possible starting lineup:
Ruiz; Lopez, Chete, Garcia, Blasco; Molina, El Ghazoui, Mohedano; Joaquinete, Bakkali, Jorge
FC Midtjylland possible starting lineup:
Olafsson; Anderson, Diao, M Sorensen, Jensen; Brynhildsen, O Sorensen, Castillo, Simsir; Buksa, Dju
We say: UE Santa Coloma 1-2 FC Midtjylland
Considering the difficulties that Santa Coloma encountered in their first-round tie against Ballkani, they could once again struggle on Tuesday.